Biopolym. Cell. 2010; 26(6):486-491.
Structure and Function of Biopolymers
Expression and subcellular localization of p70S6 kinase under
heart failure
- Institute of Molecular Biology and Genetics, NAS of Ukraine
150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680 - National Scientific Center "M. D. Strazhesko Institute of Cardiology, MAS of Ukraine"
5, Narodnogo Opolchennya Str., Kyiv, Ukraine, 03151 - Pathomorphological Laboratory "BIONTEK"
52A/88, Komsomol'ska Str., Dnipropetrovs'k, Ukraine, 49000
Abstract
The PI3K/PDK/Akt/mTOR/p70S6K signaling pathway is primary associated with the activation of insulin receptors and is important for cardiomyocytes survival. p70S6K is a key regulator of the speed and efficiency of protein biosynthesis within the cell. Recently the pro-apoptotic protein BAD has been identified as a new target for p70S6K1. BAD is inactivated in normal cardiomyocytes by p70S6K1 phosphorylation which prevents the cardiomyocytes apoptosis. Aim. To study possible changes in p70S6K1 expression and/or cellular localization at heart failure progression – in DCM-affected human myocardia and murine hearts with experimental DCM-like pathology. Methods. Western-blot analysis and immunohystochemistry. Results. The substantial decrease in p70S6K1 level was observed at the final stage of pathology progression and in the dynamics of DCM pathogenesis as well. For the first time relocalization of the protein to the connective tissue was shown according to the Western-blot results. Conclusions. The data obtained allow us to understand a possible role of p70S6K1 in the regulation of stress-induced apoptotic signaling in cardiomyocytes.
Keywords: р70S6K1, apoptosis, heart failure, Western-blotting, immunohystochemistry
Full text: (PDF, in Russian)
References
[1]
Maron B. J., Towbin J. A., Thiene G., Antzelevitch C., Corrado D., Arnett D., Moss A. J., Seidman C. E., Young J. B. An American Heart Association Scientific Statement From the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention Circulation 2006 113, N 14:1807–1816.
[2]
Hein S., Schaper J. Pathogenesis of dilated cardiomyopathy and heart failure: insights from cell morphology and biology Curr. Opin. Cardiol 1996 11, N 3:293–301.
[3]
Narula J., Haider N., Virmani R., DiSalvo T. G., Kolodgie F. D., Hajjar R. J., Schmidt U., Semigram M. J., Dec G. W., Khaw B. A. Apoptosis in myocytes in end-stage heart failure N. Engl. J. Med 1996 335, N 16:1182–1189.
[4]
Dorn G. W., 2nd. Apoptotic and non-apoptotic programmed cardiomyocyte death inventricular remodeling Cardiovasc. Res 2009 81, N 3:465–473.
[5]
Masri C., Chandrashekhar Y. Apoptosis: a potentially reversible, meta-stable state of the heart Heart Fail. Rev 2008 13, N 2:175–179.
[6]
Edinger A. L., Thompson C. B. Death by design: apoptosis, necrosis and autophagy Curr. Opin. Cell Biol 2004 16, N 6:663–669.
[7]
Reeve J. L., Duffy A. M., O'Brien T., Samali A. Don't lose heart – therapeutic value of apoptosis prevention in the treatment of cardiovascular disease J. Cell. Mol. Med 2005 9, N 3:609–622.
[8]
Valovka T. I., Gout I. T., Filonenko V. V. Effect of point mutations of regulatory aminoacids residues and N- and C-terminal deletions of S6K1 i S6K2 on kinase activity Biopolym cell. 2005. 21, N 1:42-47.
[9]
Kozma S. C., Thomas G. Regulation of cell size in growth, development and human disease: PI3K, PKB and S6K Bioessays 2002 24, N 1:65–71.
[10]
Kapustian L. M., Rozhko O. T., Bobyk V. I., Kroupska I. V., Riabenko D. V., Khozhaenko Yu. S., Gurtovyy V. A., Usenko V. S., Sidorik L. L. Changes in the content of molecular chaperone Hsp60 in heart tissue at dilated cardiomyopathy Biopolym. Cell 2008 24, N 3:238–245.
[11]
Kim S. C., Stice J. P., Chen L., Jung J. S., Gupta S., Wang Y., Baumgarten G., Trial J., Knowlton A. A. Extracellular heat shock protein 60, cardiac myocytes, and apoptosis Circ. Res 2009 105, N 12:1186–1195.
[12]
Ryabenko D. V., Sidorik L. L., Bobyk V. I., Sergienko O. V., Fedorkova O. M., Trunina I. V., Matsuka G. Kh. Morphological features of autoimmune damage of myocardium caused by various human miocardial antigens: comparative experimental examination. Ukr. Reumatol. Zhur. 2000; N 2:55–60.
[13]
Bobyk V. I., Ryabenko D. V., Sergienko O. V., Trunina I. V., Fedorkova O. M., Morozova L. M., Sidorik L. L. Experimental model of autoimmune myosin-induced myocardium injury Biopolym. Cell 2007 23, N 2:115–121.
[14]
Matsiota P., Druet P., Dosquet P., Guilbert B., Avrameas S. Natural autoantibodies in systemic lupus erythematosus. Clin. Exp. Immunol. 1987; 69(1):79–88.
[15]
Bradford M. M. A rapid and sensitive method for the quantitation of microgramm quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 1976; 72(1–2):248–254.
[16]
Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4 Nature 1970 227, N 5259:680–685.
[17]
Lie J. T., Holley K. E., Kampa W. R., Titus J. L. New histochemical method for morphologic diagnosis of early stages of myocardial ischemia Mayo. Clin. Proc 1971 46, N 5:319–327.
[18]
Cellarius Yu. G., Semenova L. A., Nepomniaschij L. M. Ochagovye povrezhdeniya i infarkt miokarda: svetovaya, poliarizatsionnaya i elektronnaya mikroskopiya: Metod. razrabotka po patolog. anatomii Novosibirsk, 1980 72 s.
[19]
Avtandilov GG, Yabluchanskiy NI, Gudenko VG. System stereometry in the pathological process study. M.: Meditsina, 1981; 191 p.
[20]
Kis A., Yellon D. M., Baxter G. F. Second window of protection following myocardial preconditioning: an essential role for PI3 kinase and p70S6 kinase J. Mol. Cell Cardiol 2003 35, N 9:1063–1071.
[21]
Harada H., Andersen J. S., Mann M., Terada N., Korsmeyer S. J. p70S6 kinase signals cell survival as well as growth, inactivating the pro-apoptotic molecule BAD Proc. Natl Acad. Sci. USA 2001 98, N 17:9666–9670.
[22]
Bobik V. I., Veberov A. V., Ryabenko D. V., Dubrovskaya G. V., Rodnin N. V., Sidorik L. L. The purification of the main tissue-specific antigens from the normal and effected by dilatative cardiomyopathia human heart Biopolym. Cell 1993 9, N 6:63–66.
[23]
Zolk O., Schenke C., Sarikas A. The ubiquitin-proteasome system: focus on the heart Cardiovasc. Res 2006 70, N 3:410–421.
[24]
Clemens M. J., van Venrooij W. J., van de Putte L. B. Apoptosis and Autoimmunity Cell Death Differ 2000 7, N 1 P. 131–133.
[25]
Kapustian L. M., Rozhko O. T., Tykhonkova I. O., Sidorik L. L. Interaction between Hsp60 and Bax in normal human myocardium and in myocardium affected by dilated cardiomyopathy Biopolym. Cell 2009 25, N 2:142–145.
[26]
Soti C., Pal C., Papp B., Csermely P. Molecular chaperons as regulatory elements of cellular networks Curr. Opin. Cell Biol 2005 17, N 2:210–215.